Home LiteratureArticle Details
PMID: 10970881 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Unproductively spliced ribosomal protein mRNAs are natural targets of mRNA surveillance in C. elegans.

Genes & development ·Vol. 14 ·No. 17 ·2000-09-01 ·Pages 2173-84

Mitrovich QM, Anderson P

Abstract

Messenger RNA surveillance, the selective and rapid degradation of mRNAs containing premature stop codons, occurs in all eukaryotes tested. The biological role of this decay pathway, however, is not well understood. To identify natural substrates of mRNA surveillance, we used a cDNA-based representational difference analysis to identify mRNAs whose abundance increases in Caenorhabditis elegans smg(-) mutants, which are deficient for mRNA surveillance. Alternatively spliced mRNAs of genes encoding ribosomal proteins L3, L7a, L10a, and L12 are abundant natural targets of mRNA surveillance. Each of these genes expresses two distinct mRNAs. A productively spliced mRNA, whose abundance does not change in smg(-) mutants, encodes a normal, full-length, ribosomal protein. An unproductively spliced mRNA, whose abundance increases dramatically in smg(-) mutants, contains premature stop codons because of incomplete removal of an alternatively spliced intron. In transgenic animals expressing elevated quantities of RPL-12, a greater proportion of endogenous rpl-12 transcript is spliced unproductively. Thus, RPL-12 appears to autoregulate its own splicing, with unproductively spliced mRNAs being degraded by mRNA surveillance. We demonstrate further that alternative splicing of rpl introns is conserved among widely diverged nematodes. Our results suggest that one important role of mRNA surveillance is to eliminate unproductive by-products of gene regulation.

MeSH Terms
Alternative Splicing Animals Animals, Genetically Modified Base Sequence Blotting, Northern Caenorhabditis/genetics Caenorhabditis elegans/genetics Cloning, Molecular Codon DNA, Complementary/metabolism Exons Introns Models, Genetic Molecular Sequence Data Mutagenesis, Site-Directed RNA Splicing RNA, Messenger/metabolism Ribosomal Proteins/genetics Ribosomes/metabolism Sequence Homology, Nucleic Acid Transformation, Genetic
Chemicals
Codon DNA, Complementary RNA, Messenger Ribosomal Proteins
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mitrovich Q M
Department of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA.
Anderson P
References (44)
44 references, click to expand
  1. An internal open reading frame triggers nonsense-mediated decay of the yeast SPT10 mRNA.
    EMBO J. 1999 Nov 1;18(21):6134-45 PMID: 10545123
  2. Yeast Upf proteins required for RNA surveillance affect global expression of the yeast transcriptome.
    Mol Cell Biol. 1999 Oct;19(10):6710-9 PMID: 10490610
  3. The Caenorhabditis elegans rol-6 gene, which interacts with the sqt-1 collagen gene to determine organismal morphology, encodes a collagen.
    Mol Cell Biol. 1990 May;10(5):2081-9 PMID: 1970117
  4. NAM7 nuclear gene encodes a novel member of a family of helicases with a Zn-ligand motif and is involved in mitochondrial functions in Saccharomyces cerevisiae.
    J Mol Biol. 1992 Apr 5;224(3):575-87 PMID: 1314899
  5. Gene products that promote mRNA turnover in Saccharomyces cerevisiae.
    Mol Cell Biol. 1992 May;12(5):2165-77 PMID: 1569946
  6. Independent domains of the Sdc-3 protein control sex determination and dosage compensation in C. elegans.
    Cell. 1993 Feb 12;72(3):349-64 PMID: 8431944
  7. Stabilization and ribosome association of unspliced pre-mRNAs in a yeast upf1- mutant.
    Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7034-8 PMID: 8346213
  8. mRNA surveillance by the Caenorhabditis elegans smg genes.
    Genes Dev. 1993 Oct;7(10):1885-97 PMID: 8104846
  9. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14.
    Cell. 1993 Dec 3;75(5):843-54 PMID: 8252621
  10. Regulation of splicing at an intermediate step in the formation of the spliceosome.
    Genes Dev. 1994 Jan;8(2):211-20 PMID: 8299940
  11. Structure and evolution of a member of a new subfamily of GTP-binding proteins mapping to the human MHC class I region.
    Mamm Genome. 1994 Feb;5(2):100-5 PMID: 8180467
  12. Identifying differences in mRNA expression by representational difference analysis of cDNA.
    Nucleic Acids Res. 1994 Dec 25;22(25):5640-8 PMID: 7838717
  13. 18S ribosomal RNA gene phylogeny for some Rhabditidae related to Caenorhabditis.
    Mol Biol Evol. 1995 Mar;12(2):346-58 PMID: 7700158
  14. Feedback inhibition of the yeast ribosomal protein gene CRY2 is mediated by the nucleotide sequence and secondary structure of CRY2 pre-mRNA.
    Mol Cell Biol. 1995 Nov;15(11):6454-64 PMID: 7565797
  15. The small nucleolar RNAs.
    Annu Rev Biochem. 1995;64:897-934 PMID: 7574504
  16. Representational difference analysis in detection of genetic lesions in cancer.
    Methods Enzymol. 1995;254:291-304 PMID: 8531693
  17. A regulatory mechanism that detects premature nonsense codons in T-cell receptor transcripts in vivo is reversed by protein synthesis inhibitors in vitro.
    J Biol Chem. 1995 Dec 1;270(48):28995-9003 PMID: 7499432
  18. Basic culture methods.
    Methods Cell Biol. 1995;48:3-29 PMID: 8531730
  19. DNA transformation.
    Methods Cell Biol. 1995;48:451-82 PMID: 8531738
  20. Mammalian orthologues of a yeast regulator of nonsense transcript stability.
    Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10928-32 PMID: 8855285
  21. Analysis of yeast trimethylguanosine-capped RNAs by midwestern blotting.
    Gene. 1996 Dec 5;182(1-2):89-96 PMID: 8982072
  22. Binding of mammalian ribosomal protein complex P0.P1.P2 and protein L12 to the GTPase-associated domain of 28 S ribosomal RNA and effect on the accessibility to anti-28 S RNA autoantibody.
    J Biol Chem. 1997 Feb 7;272(6):3302-8 PMID: 9013569
  23. smg mutants affect the expression of alternatively spliced SR protein mRNAs in Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9782-5 PMID: 9275202
  24. The splicing factor SRp20 modifies splicing of its own mRNA and ASF/SF2 antagonizes this regulation.
    EMBO J. 1997 Aug 15;16(16):5077-85 PMID: 9305649
  25. A molecular evolutionary framework for the phylum Nematoda.
    Nature. 1998 Mar 5;392(6671):71-5 PMID: 9510248
  26. Selenium deficiency reduces the abundance of mRNA for Se-dependent glutathione peroxidase 1 by a UGA-dependent mechanism likely to be nonsense codon-mediated decay of cytoplasmic mRNA.
    Mol Cell Biol. 1998 May;18(5):2932-9 PMID: 9566912
  27. A mutated human homologue to yeast Upf1 protein has a dominant-negative effect on the decay of nonsense-containing mRNAs in mammalian cells.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10009-14 PMID: 9707591
  28. mRNA surveillance mitigates genetic dominance in Caenorhabditis elegans.
    Mol Gen Genet. 1998 Nov;260(2-3):176-84 PMID: 9862469
  29. smg-7 is required for mRNA surveillance in Caenorhabditis elegans.
    Genetics. 1999 Feb;151(2):605-16 PMID: 9927455
  30. The intronerator: exploring introns and alternative splicing in Caenorhabditis elegans.
    Nucleic Acids Res. 2000 Jan 1;28(1):91-3 PMID: 10592190
  31. Mechanisms of mRNA surveillance in eukaryotes.
    Annu Rev Genet. 1999;33:229-60 PMID: 10690409
  32. Genomic sequencing.
    Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5 PMID: 6326095
  33. Regulation of the synthesis of ribosomes and ribosomal components.
    Annu Rev Biochem. 1984;53:75-117 PMID: 6206783
  34. Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse.
    EMBO J. 1985 Feb;4(2):351-9 PMID: 3926482
  35. Site-directed cleavage of RNA.
    Nucleic Acids Res. 1987 Jun 11;15(11):4403-15 PMID: 2438655
  36. Second-strand cDNA synthesis: mRNA fragments as primers.
    Methods Enzymol. 1987;152:330-5 PMID: 3309563
  37. Optimal alignments in linear space.
    Comput Appl Biosci. 1988 Mar;4(1):11-7 PMID: 3382986
  38. Fast and sensitive multiple sequence alignments on a microcomputer.
    Comput Appl Biosci. 1989 Apr;5(2):151-3 PMID: 2720464
  39. A new kind of informational suppression in the nematode Caenorhabditis elegans.
    Genetics. 1989 Oct;123(2):301-13 PMID: 2583479
  40. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure.
    J Mol Biol. 1999 May 21;288(5):911-40 PMID: 10329189
  41. Determinants of SR protein specificity.
    Curr Opin Cell Biol. 1999 Jun;11(3):358-62 PMID: 10395560
  42. Should we kill the messenger? The role of the surveillance complex in translation termination and mRNA turnover.
    Bioessays. 1999 Aug;21(8):685-96 PMID: 10440865
  43. SMG-2 is a phosphorylated protein required for mRNA surveillance in Caenorhabditis elegans and related to Upf1p of yeast.
    Mol Cell Biol. 1999 Sep;19(9):5943-51 PMID: 10454541
  44. Functions of the myosin ATP and actin binding sites are required for C. elegans thick filament assembly.
    Cell. 1990 Jan 12;60(1):133-40 PMID: 2136805
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.819900
Published
2000-09-01
Pages
2173-84
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316897
Subset
IM
Grants
NIGMS NIH HHS · R01 GM050933 · United States
NIGMS NIH HHS · GM50933 · United States
External Links
PubMed source DOI: 10.1101/gad.819900 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2